Differences in the Long-term Impact of the COVID-19 Pandemic on the Mental Health and Professional Quality of Life of Resident and Specialist Physicians.

BACKGROUND: The COVID-19 pandemic created an extremely difficult situation for healthcare workers (HCWs) worldwide. We aimed to compare the mental health and professional quality of life of residents and specialist physicians in a cohort of Italian HCWs caring for patients with COVID-19 about two years after the start of the COVID-19 pandemic. METHODS: In November 2021, an online survey investigating the emotional states of depression, anxiety, stress, compassion satisfaction and compassion fatigue was administered to HCWs (N= 78) at the Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome. RESULTS: Our findings suggest that from 5 to 20% of our cohort of HCWs still showed the effects of the adverse psychological impact of the pandemic and more than half of them experienced medium levels of compassion fatigue as well as a medium level of compassion satisfaction. Our results also show that those with fewer years of clinical practice might be at greater risk of burnout (p= 0.021), anxiety and stress symptoms (both ps= 0.027) and might develop a lower level of compassion satisfaction (p=0.018). Moreover, the factors that potentially contribute to poor mental health, compassion fatigue and compassion satisfaction seem to differ between residents and specialist physicians. CONCLUSIONS: This overview presents one of the first pictures of the long-term effects of the pandemic on the mental health and professional quality of life of an Italian sample of HCWs. Moreover, it also helps identify professionals who are most in need of support and emphasises the importance of improving the psychological and professional wellbeing of these individuals especially during a pandemic-like crisis with long lasting effects.

HIV-Related Internalized Stigma and Patient Health Engagement Model in an Italian Cohort of People Living With HIV.

The care engagement of people living with HIV (PLWH) measured with the patient health engagement (PHE) model and its association with HIV-related internalized stigma are not well established. Indeed, currently there are no data yet about the engagement of PLWH measured with the PHE model. This study aimed to evaluate the effects of HIV-related internalized stigma on care engagement and mental health and to fill the lack of data on PHE model applied to PLWH. We found that the internalized stigma score was significantly higher for PLWH (n=82) in worse care engagement phase and both higher internalized stigma scores and worse engagement were associated to major depression symptoms.In conclusion, our findings describe for the first time the engagement in care of PLWH measured with PHE and highlight the importance of PLWH support to find strategies to cope stigma-related stress and optimize their care engagement.

Difference in the neurocognitive functions of WLWH and MLWH in an Italian cohort of people living with HIV.

Based on the available literature, women living with HIV (WLWH) seem to show greater cognitive and emotional disadvantages than men living with HIV (MLWH). Our aim was to compare the cognitive performance of MLWH and WLWH in an Italian cohort of People Living With HIV (PLWH) and to analyse factors potentially contributing to sex differences in cognitive function. We ran a retrospective, cross-sectional analysis of a monocentric dataset of PLWH who were administered a standardized neuropsychological test battery (SNB) during routine clinical care. We enrolled 161 Italian PLWH who are on combined antiretroviral therapy (cART): 114 (70.8%) MLWH and 47 (29.2%) WLWH.Global cognitive performance (composite z score) (GCP) was significantly higher in MLWH than WLWH [mean 0.19 (SD 0.85) vs - 0.13 (SD 0.96); p = 0.039]. Moreover, WLWH obtained significantly higher scores on the Zung Depression Scale than MLWH [mean 41.8 (SD 10.9) vs 36.7 (SD 9.2); p = 0.003]. However, there was no statistically significant direct effect between male sex and better GCP (p = 0.692) in the context of a mediation model. On the contrary, the associations between male sex and better GCP were mediated by higher level of education (a*b = + 0.15, Bootstrap CI95 = 0.05 and 0.27) and a lower Zung depression score (a*b = + 0.10, Bootstrap CI95 = 0.02 and 0.21).In conclusion, the global cognitive performance of WLWH is lower than that of MLWH. However, other demographic and clinical factors besides sex might help explain differences in their neurocognitive functions and make it possible for us to monitor them and identify those patients most in need.

The facial emotion recognition deficit in Parkinson's disease: Implications of a visual scanning strategy.

OBJECTIVE: We explored the relationship between a visual scanning strategy and a facial emotion recognition deficit in Parkinson's disease (PD). METHOD: Thirty nondemented PD patients (balanced for symptom side at onset) and 20 age, education and gender-matched healthy controls (HC) were enrolled. The PD group underwent a comprehensive neuropsychological battery also exploring the executive functions. In both groups, eye movements were recorded while subjects categorized facial emotion from Ekman's 60-faces test. We were particularly interested in the location of fixations on facial pictures (top vs. bottom) and in emotional valence (positive vs. negative). We also compared performance of the two groups on a verbal emotion attribution task. RESULTS: Compared to HC, PD patients performed worse on visual recognition of negative emotions such as anger, fear, and sadness (where the upper part of the face is more informative than the lower part); the two groups did not differ on the verbal emotion attribution task. HC modified their visual scanning strategy (both number and overall time duration of fixations) according to the valence of the emotion; by contrast, PD showed the same pattern regardless of the valence. In the PD group, accuracy in the visual recognition of negative emotions and fixation pattern correlated with performance on tasks exploring executive functions; however, no associations were observed with severity of motor state. CONCLUSIONS: Our results suggest that visual scanning strategy contributes significantly to the facial emotion recognition deficit of PD patients, especially at a "high level" related to cognitive control of eye movements. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Writing errors in primary progressive aphasia.

Peripheral errors in writing, that is errors produced download the spelling, have been occasionally described in primary progressive aphasia (PPA), but the possibility that these errors might be a marker of parkinsonism associated to some subtypes of PPA has not been explored. We investigated whether errors of peripheral nature characterize the writing disorder in PPA when associated with parkinsonian signs (PSs). Subgroups of PPA without PSs and with PSs were studied. The proportion of the central and peripheral errors in writing words and pseudowords was calculated in each group. In writing words, central errors significantly exceeded peripheral errors in subgroups without PSs. The higher the number of peripheral errors, the higher the probability of presenting PSs. No relation emerged between any error and the Unified Parkinson's Disease Rating Scale, but both types of errors correlated with measures of cognitive ability. Peripheral errors emerge when PSs are associated with PPA and may be linked to a decay of the cognitive control on movement, possibly involving the right hemisphere. Peripheral errors have clinical relevance in PPA, to the extent that they may assume the significance of a marker of specific subtypes and can help to outline the specific clinical picture of individual patients.

Cognitive reserve: a multidimensional protective factor in Parkinson's disease related cognitive impairment.

We explored the association between cognitive reserve (CR) and Parkinson' s disease (PD) related cognitive deterioration.Forty PD patients and 12 matched healthy controls (HC) were enrolled. The PD group was balanced for the presence/absence of cognitive impairment. All participants underwent MOCA. CR was measured by the Brief Intelligence Test, and a new comprehensive tool, named Cognitive Reserve Test (CoRe-T), including sections on leisure activities and creativity.Participants with higher CR obtained a better MOCA score irrespective of the group they belonged to. At the same time, irrespective of the CR level, the performance of the HC group was always better in comparison to the PD group. Within the PD group, a higher frequency of leisure activities was associated to be cognitively unimpaired, independently by the severity of motor symptoms and age.CR could help to cope with PD-related cognitive decline. Its multidimensional nature could have important applications in prevention and rehabilitation interventions.

Use of telehealth for HIV care in Italy: Are doctors and patients on the same page? A cross-sectional study.

BACKGROUND: The COVID-19 pandemic has changed outpatient clinical practice, which has led to the need defining digital healthcare modalities to provide telehealth services. The aim of our study was to explore opinions about HIV management via telehealth in a representative, southern central Italian cohort of individuals with HIV (PLWH) and doctors involved in the treatment process. METHODS: We enrolled 80 PLWH who have never used telehealth tools and 60 doctors, who administered an anonymous self-report questionnaire to investigate their opinions about telehealth service use. RESULTS: Most of the doctors and patients indicated that they would use telehealth services; however, 88.3% of the doctors and 40% of the PLWH did not want to substitute personal visits with telehealth services. Unlike PLWH, physicians seemed to agree with most of the possible risks of telehealth, such as patients' isolation from the hospital system (71.7%), interaction difficulty (46.7%) and lower quality of patient assessment (63.3%). The doctors focused on the qualitative aspects of telehealth services reducing patients' exposure to stigma (61.7%), improving quality of patient care (41.7%), and improving privacy (58.3%). By contrast, patients focused on the quantitative aspects of telehealth services improving timely access to care (44%), time saving (63%) and improving interaction with doctor (43%). CONCLUSIONS: Both PLWH (especially older patients and those with longer experience of disease management) and doctors welcome the use of telehealth services but disagree using it to substitute medical consultation in person focusing on different possible benefits and risks of telehealth depending on the needs expressed. Thus, our results suggest the need to initiate and expand communication about telehealth between doctors and patients.

Psychological distress during the initial stage of the COVID-19 pandemic in an Italian population living with HIV: an online survey.

The aim of this study was to explore the psychological impact of the initial stage of the 2019 coronavirus (COVID-19) pandemic on people living with HIV (PLWH), a population at increased risk of psychological distress. PLWH participated in an online survey exploring demographic and clinical data, physical symptoms, contact history, knowledge and concerns, precautionary measures and additional information about COVID-19 during the first phase of the pandemic in Italy. The Impact of Event Scale-Revised (IES-R) (identifying the COVID-19 pandemic as a specific traumatic life event) and the Depression, Anxiety and Stress Scale (DASS-21) also formed part of the survey. Out of 98 participants, 45% revealed from mild to severe psychological impact from COVID-19 according to IES-R. A lower percentage, instead, complained of significant levels of depression (14%), anxiety (11%) or stress (6%) according to DASS-21. Higher education, being unemployed, number of perceived COVID-19 physical symptoms, concerns about risk of contracting COVID-19 and the pandemic situation in Italy, and needing additional information to prevent COVID-19 infection were positively associated to a higher risk of negative psychological impact. Moreover, among the participants, female gender, age, fewer years from HIV diagnosis and not being aware of their own viremia were associated to a higher risk of negative psychological outcomes. Almost half of our PLWH sample experienced significant levels of distress related to the COVID-19 pandemic. Women, elderly patients and those with recent HIV diagnosis appear to be the more psychologically fragile subgroups. Our findings could help identify patients most in need of psychological interventions to improve the wellbeing of PLWH.

The University of California San Diego performance-based skills assessment: a useful tool to detect mild everyday functioning difficulties in HIV-infected patients with very good immunological condition.

Everyday functioning (EF) impairment is frequent in people living with HIV (PLWH). Our aim was to better explore EF and its association with PLWH cognition, by administering both the IADL scale, the most common functional scale, and a new and ecologic multi-domain (communication and financial skills) tool to measure EF as the University of California San Diego (UCSD) Performance-Based Skills Assessment-Brief Version (UPSA-B). Eighty-five PLWH on cART with very good immunological condition and 23 age- and education-matched healthy controls (HC) were enrolled. PLWH underwent a standardized neuropsychological battery plus IADL, and cognitive impairment was defined according to Frascati criteria. Both groups underwent the UPSA-B. Only 6 subjects (7%) were affected by cognitive impairment (asymptomatic profile). While IADL score was at ceiling for all patients, the UPSA-B total score was significantly worse in PLWH when compared with HC [mean 82.1 (SD 9.3) vs 89.2 (SD 6.2); p < 0.001]. At communication subtest, PLWH group and HC were significantly different (p = 0.002), while no difference emerged at financial skills (p = 0.096). Higher score at UPSA-B was independently associated with better global cognitive performance (composite Z-score) (ß 7.79; p < 0.001). Also considering each single cognitive domain, UPSA-B performance (both total and at subtests) confirmed the association with neurocognitive performance. In conclusion, UPSA-B seems to better discriminate EF impairment than IADL in PLWH, and it was associated with cognitive functions, also in the absence of symptomatic cognitive impairment. Thus, it appears a promising tool in the context of HIV infection to avoid misdiagnosis and to better detect also mild EF.

Considerations on nosology for HIV-associated neurocognitive disorders: it is time to update?

AIMS: The prognosis and the clinical manifestations of HIV infection have changed with the introduction of the potent combination antiretroviral therapy (cART); however, up to 50% of patients meet research criteria for "HIV-associated neurocognitive disorders" (HAND) according with current nosology. The majority of patients affected by HAND, especially in cohorts with suppressed plasma viremia, showed an Asymptomatic Neurocognitive Impairment (ANI), without any functional impairment. After more than 10 years from the introduction of the current so-called "Frascati criteria", this mini-review aimed to address the emerging limitations in current diagnosis procedures. METHODS: We discussed the most relevant literature on HAND prevalence, etiology, and diagnosis. RESULTS: We addressed three main emerging issues: (1) the unclear clinical relevance of ANI entity; (2) the evidences that Frascati criteria could produce a significant overestimation of HAND; (3) the need to better identify patients with a higher risk to develop HAND requiring routine neuropsychological examinations. CONCLUSIONS: Frascati criteria should be updated to better respond to the present characteristics of HIV + cohorts and to help clinicians in their cognitive and global management.

Degenerative and Vascular Fluent Aphasia: Looking for Differences.

OBJECTIVE: To investigate whether the characteristics of language disorders of degenerative and vascular aphasias depend on the underlying neuropathology. METHODS: Logopenic variant/mixed primary progressive aphasics (lvmPPA; n=18) and poststroke fluent aphasics (PSA; n=11) underwent a neuropsychological examination and an assessment of the macro- and microlinguistic aspects of language. A principal component analysis and a cluster analysis applying a two-group solution were performed on the scores obtained from the neuropsychological and language examination. RESULTS: Global cognition, lexical-semantic, and morphosyntactic components, and two components loading macrolinguistic variables, were extracted by the principal component analysis. A first cluster of 18 participants (14 lvmPPA and 4 PSA) and a second cluster of 11 participants (4 lvmPPA and 7 PSA) were identified. Participants in the first cluster were significantly more impaired than those in the second cluster in global cognition, lexical-semantic, and morphosyntactic components. Macrolinguistic components did not differentiate the two clusters. lvmPPA in the first cluster showed bilateral cortical thinning (greater on the left), whereas lvmPPA in the second cluster showed atrophy only in the left. Participants with PSA in both clusters showed vascular lesions encompassing the posterior left perisylvian regions. Underestimation of the severity of the leukoencephalopathy and damage of the interhemispheric connectivity might be responsible for the inclusion of PSA individuals in the first cluster, despite a unilateral lesion. CONCLUSIONS: Lesion localization is the main factor that determines the characteristics of aphasic deficits. Etiology indirectly acts through a different sensitivity of the brain regions to various pathologies.

Cognitive impairment and cardiovascular disease related to alexithymia in a well-controlled HIV-infected population.

Both cognitive diseases and alexithymia may be associated with HIV. Moreover, alexithymia has been linked to cardiovascular (CV) diseases. Our aim was to explore the prevalence of alexithymia and its associations with neurocognitive disorders (HAND) and CV risk factors in a well-controlled HIV-positive population. We consecutively enrolled 140 HIV-positive individuals on antiretroviral therapy and 35 healthy subjects matched for age, education and gender. In all participants alexithymia was explored by the 20-item Toronto Alexithymia Scale. For HIV-positive subjects also data about CV risk factors were collected, and a comprehensive neuropsychological examination was administered; HAND was defined according to Frascati criteria. Patients and controls did not differ in the proportion of alexithymic status (10% vs. 11%; p=0.761). Among HIV-positive patients, alexithymic participants presented a higher prevalence of diabetes (21% vs. 3%, p=0.035) and hypertension (36% vs. 13%, p= 0.037) compared to non-alexithymic. About 30% (n=41) of HIV-positive patients met criteria for asymptomatic HAND. Alexithymia was not independently associated with a higher risk of HAND (p=0.189). Analyzing each cognitive domain, alexithymia showed an independent association with an abnormal performance (OR 1.08; p=0.037) only in psychomotor speed. In conclusion, in the context of a well-controlled HIV infection, we found a low prevalence of alexithymia comparable to healthy controls. Alexithymia was linked to higher risk of CV disease in the HIV-positive population, but with a rate similar to that previously estimated in the HIV-negative alexithymic. Finally, alexithymia was clearly associated to cognitive impairment only in the psychomotor speed domain, suggesting a common fronto-striatal system dysregulation.

Hepatitis C virus-related factors associated WITH cognitive performance in HIV-HCV-coinfected patients.

The contribution of HCV-related variables to cognitive impairment in HIV-HCV-coinfected patients has been poorly investigated. We selected HIV-HCV-coinfected patients undergoing cognitive examination (exploring memory, language, speed of mental processing and fine motor function) at three clinical centres. Cognitive performance was evaluated using Z-transformed scores. Logistic regression analysis was used to investigate variables associated to cognitive impairment (defined as a composite Z-score ≤ - 1). Overall, 146 HIV-HCV-coinfected patients were enrolled. Median HCV-RNA was 6.2logU/mL. HCV genotype 1a/b was the most represented (53.4%). Liver fibrosis was mild (Fib4 ≤ 1.45) in the majority of patients (44.5%). Global cognitive impairment was diagnosed in 35 (24%) subjects. Exploring each domain, a higher proportion of impairment was observed for memory (37%) followed by speed of mental processing (32.2%), fine motor functioning (24%) and language (18.5%). Among HCV-related variables, the duration of HCV infection was independently associated with global cognitive impairment (aOR 1.13 per +1 year, p = 0.016) and abnormal speed of mental processing (aOR 1.16 per +1 year, p = 0.001), while higher HCV-RNA was independently associated to fine motor functioning impairment (aOR 1.98 per +1log, p = 0.037). HCV genotype, fibrosis stage, transaminases or bilirubin levels were not related to cognitive performance. Of note, integrase inhibitor (InSTI) use was independently associated to a pathological performance in fine motor functioning (aOR 3.34, p = 0.035) and memory (aOR 3.70, p = 0.014). In conclusion, the duration of HCV infection and HCV-RNA load showed an association with cognitive impairment, suggesting a role of hepatitis-related factors in the development of cognitive disorders in HIV-HCV-coinfected patients. The association between InSTI use and altered cognitive performance should prompt investigations about potential neurotoxicity of these drugs.

Emotional valence may influence memory performance for visual artworks in Parkinson's disease.

BACKGROUND: Non-motor symptoms in Parkinson's disease (PD) include reduced reactivity to emotional stimuli. Visual artworks can evoke emotional responses. Motor, sensorial and cognitive networks implicated in the aesthetic experience and in the emotional-reward domain show a significant overlap with the pathological nigrostriatal, mesocortical and mesolimbic circuitry that characterises PD. METHODS: Memory enhancement by emotional stimuli such as visual artwork-stimuli was explored in 12 right-sided and 12 left-sided non-demented-PD patients, 12 Alzheimer's disease patients (AD) and 13 healthy controls (HC). Ten emotional and 10 non-emotional stimuli were previously identified based on the ratings of the emotional impact provided by 45 non-PD subjects on 82 pictures of paintings. Only figurative artworks were included. Patients and HC were requested to rate on a 7-point scale the emotional impact of 20 pictures; they were then requested to recognise the 20 pictures amongst 20 distractors (incidental memory task). RESULTS AND CONCLUSION: Recognition of emotional stimuli was more accurate compared to non-emotional stimuli in AD, left-sided PD and HC; right-sided PD did not show sensitivity to the emotional valence of the stimuli suggesting the involvement of the nigrostriatal, mesocortical and mesolimbic circuitry of the left hemisphere in the emotional-reward system related to the aesthetic experience.

Liver fibrosis is associated with cognitive impairment in people living with HIV.

PURPOSE: Our aim was to better explore the association between liver fibrosis (LF) and neurocognitive impairment (NCI) in people living with HIV (PLWH). METHODS: We performed a cross-sectional cohort study by consecutively enrolling PLWH at two clinical centers. All subjects underwent a comprehensive neuropsychological battery; NCI was defined as having a pathological performance (1.5 SD below the normative mean) on at least two cognitive domains. LF was explored using FIB4 index; in a subgroup of PLWH, LF was also assessed by transient elastography. RESULTS: A total of 386 subjects were enrolled, of whom 17 (4.4%) had FIB4 > 3.25. In the subgroup of PLWH (N = 127) performing also liver transient elastography, 14 (11%) had liver stiffness > 14 kPa. Overall, 47 subjects (12%) were diagnosed with NCI. At multivariate regression analyses, participants with FIB4 > 1.45 showed a higher risk of NCI in comparison with those with lower values (aOR 3.04, p = 0.044), after adjusting for education (aOR 0.71, p < 0.001), past AIDS-defining events (aOR 2.91, p = 0.014), CD4 cell count, past injecting drug use (IDU), HIV-RNA < 50 copies/mL, and HCV co-infection. Also a liver stiffness > 14 kPa showed an independent association with a higher risk of NCI (aOR 10.13, p = 0.041). Analyzing any single cognitive domain, a higher risk of abnormal psychomotor speed was associated with a liver stiffness > 14 kPa (aOR 223.17, p = 0.019) after adjusting for education (aOR 0.57, p = 0.018), HIV-RNA < 50 copies/mL (aOR 0.01, p = 0.007), age, past IDU, and HCV co-infection. CONCLUSIONS: In PLWH, increased LF, estimated through non-invasive methods, was associated to a higher risk of NCI independently from HCV status.

Atazanavir/ritonavir with lamivudine as maintenance therapy in virologically suppressed HIV-infected patients: 96 week outcomes of a randomized trial.

Objectives: To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with atazanavir/ritonavir + 2NRTI in virologically suppressed patients. Methods: ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin -12%) trial enrolling HIV-infected adults on atazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364. Results: Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3-4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms. Conclusions: In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.

The role of cognitive reserve in cognitive aging: what we can learn from Parkinson's disease.

Parkinson's disease (PD) typically occurs in elderly people and some degree of cognitive impairment is usually present. Cognitive reserve (CR) theory was proposed to explain the discrepancy between the degree of brain pathologies and clinical manifestations. We administered a comprehensive neuropsychological battery to 35 non-demented participants affected by PD. All participants underwent also the Cognitive Reserve Index questionnaire and the Brief Intelligence Test as proxies for CR. Relationships between CR and cognitive performance were investigated by linear regression analyses, adjusting for significant confounding factors. At linear regression analyses, higher CR scores were independently associated with a better performance on Word Fluency (p ≤ 0.04) and Digit Span (backward) (p ≤ 0.02); no associations were observed between CR and other cognitive tests. Our data provide empirical support to the relation between CR and cognitive impairment in PD. In particular, this study suggests that CR may have greater effects on the cognitive areas mostly affected in PD as executive functions.

Total cellular HIV-1 DNA decreases after switching to raltegravir-based regimens in patients with suppressed HIV-1 RNA.

BACKGROUND: The integrase inhibitor raltegravir has been used to intensify antiretroviral therapy in patients with undetectable plasma HIV-1RNA, resulting in variable perturbation of HIV-1 nucleic acids levels in peripheral blood. OBJECTIVES: We aimed at monitoring residual plasma HIV-1RNA and total cellular HIV-1DNA in virologically suppressed patients switching to raltegravir-based regimens. STUDY DESIGN: Fifty-eight subjects on protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens, with plasma HIV-1RNA levels <40 copies/ml for ≥6 months and CD4 counts >200cells/µl for ≥12 months were enrolled. Thirty-four patients were from the treatment simplification RASTA randomized study switching standard therapy to a raltegravir-based regimen (RASTA group), while 24 continued a PI or NNRTI based-regimen (controls). Residual plasma HIV-1RNA (5-40copies/mL) and HIV-1DNA were assessed at 0, 24 and 48 weeks. RESULTS: At week 0 (W0), HIV-1DNA was detected in all patients while at W48 it was detectable in 82.4% of the RASTA group vs 100% of controls (p=0.03). There was a significant decline of HIV-1DNA at W48 in the RASTA group (mean change from baseline -0.21 [95% CI -0.41; -0.01] log10 copies/106 CD4; p=0.03) but not in controls. Ultrasensitive HIV-1RNA was detectable at baseline in 50% of RASTA group vs 67% of controls and at W48 in 32.4% vs 42%, respectively. No differences were found between HIV-1RNA levels at baseline and W48 within and between groups. CONCLUSIONS: Switching successful therapy to raltegravir-based regimens may be associated with a decrease of the HIV-1 reservoir, as measured by peripheral blood cellular HIV-1DNA levels.

Treatment simplification to atazanavir/ritonavir + lamivudine versus maintenance of atazanavir/ritonavir + two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M).

Background: Combination ART (cART)-related toxicities and costs have prompted the need for treatment simplification. The ATLAS-M trial explored 48 week non-inferior efficacy of simplification to atazanavir/ritonavir  +  lamivudine versus maintaining three-drug atazanavir/ritonavir-based cART in virologically suppressed patients. Methods: We performed an open-label, multicentre, randomized, non-inferiority study, enrolling HIV-infected adults on atazanavir/ritonavir + two NRTIs, with stable HIV-RNA <50 copies/mL and CD4 + >200 cells/mm 3 . Main exclusion criteria were hepatitis B virus coinfection, past virological failure on or resistance to study drugs, recent AIDS and pregnancy. Patients were randomly assigned 1:1 to either switch to 300 mg of atazanavir/100 mg of ritonavir once daily and 300 mg of lamivudine once daily (atazanavir/ritonavir + lamivudine arm) or to continue the previous regimen (atazanavir/ritonavir + two NRTIs arm). The primary study outcome was the maintenance of HIV-RNA <50 copies/mL at week 48 of the ITT-exposed (ITT-e) analysis with switch = failure. The non-inferiority margin was 12%. This study is registered at ClinicalTrials.gov, number NCT01599364. Results: Between July 2011 and June 2014, 266 patients were randomized (133 to each arm). After 48 weeks, the primary study outcome was met by 119 of 133 patients (89.5%) in the atazanavir/ritonavir + lamivudine arm and 106 of 133 patients (79.7%) in the atazanavir/ritonavir + two NRTIs arm [difference atazanavir/ritonavir + lamivudine versus atazanavir/ritonavir + two NRTIs arm: +9.8% (95% CI + 1.2 to + 18.4)], demonstrating non-inferiority and superior efficacy of the atazanavir/ritonavir + lamivudine arm. Virological failure occurred in two (1.5%) patients in the atazanavir/ritonavir + lamivudine arm and six (4.5%) patients in the atazanavir/ritonavir + two NRTIs arm, without resistance selection. A similar proportion of adverse events occurred in both arms. Conclusions: Treatment simplification to atazanavir/ritonavir + lamivudine showed non-inferior efficacy (superiority on post-hoc analysis) and a comparable safety profile over continuing atazanavir/ritonavir + two NRTIs in virologically suppressed patients.